RNA m6A mediates de novo DNA methylation and heritable epigenetic silencing in human cells
Abstract
DNA methylation is the most abundant epigenetic modification on the human genome and changes dynamically during embryogenesis, aging, and disease. How DNA methylation is established de novo remains incompletely understood. Using orthogonal CRISPR platforms to initiate de novo DNA methylation coupled with genome-wide CRISPR screens and proximity-dependent proteomics, we discover the interplay between RNA m6A modifications and de novo DNA methylation to program heritable epigenetic memory in human cells. The RNA m6A writer complex is recruited to chromatin with DNA methyltransferases and histone repressors during the transient establishment phase of heritable epigenetic silencing. Inhibition of RNA m6A during early pluripotent transition leads to defects in de novo DNA methylation, resulting in upregulation of transposable elements that pose a threat to genome integrity during early development. Our work reveals the vital coordination between the epitranscriptome and de novo DNA methylation to establish proper heritable epigenetic silencing in human cells.
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BibTeX
@misc{divekar2026mediates,
title = {{RNA m6A mediates de novo DNA methylation and heritable epigenetic silencing in human cells}},
author = {N. S. Divekar and N. T. Phan and L. G. Palma and J. P. Lubin and A. E. Christenson and S. C. Ulloa and P. J. Colias and D. Xu and J. Liu and S. Mukhopadhyay and B. D. Moreno and A. S. Lee and S. E. Chasins and J. K. Nunez},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.760774},
url = {https://www.biorxiv.org/content/10.64898/2026.10.21.760774v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - RNA m6A mediates de novo DNA methylation and heritable epigenetic silencing in human cells
AU - N. S. Divekar
AU - N. T. Phan
AU - L. G. Palma
AU - J. P. Lubin
AU - A. E. Christenson
AU - S. C. Ulloa
AU - P. J. Colias
AU - D. Xu
AU - J. Liu
AU - S. Mukhopadhyay
AU - B. D. Moreno
AU - A. S. Lee
AU - S. E. Chasins
AU - J. K. Nunez
PY - 2026
DA - 2026/10/21
PB - bioRxiv
DO - 10.64898/2026.10.21.760774
UR - https://www.biorxiv.org/content/10.64898/2026.10.21.760774v1
AB - DNA methylation is the most abundant epigenetic modification on the human genome and changes dynamically during embryogenesis, aging, and disease. How DNA methylation is established de novo remains incompletely understood. Using orthogonal CRISPR platforms to initiate de novo DNA methylation coupled with genome-wide CRISPR screens and proximity-dependent proteomics, we discover the interplay between RNA m6A modifications and de novo DNA methylation to program heritable epigenetic memory in human cells. The RNA m6A writer complex is recruited to chromatin with DNA methyltransferases and histone repressors during the transient establishment phase of heritable epigenetic silencing. Inhibition of RNA m6A during early pluripotent transition leads to defects in de novo DNA methylation, resulting in upregulation of transposable elements that pose a threat to genome integrity during early development. Our work reveals the vital coordination between the epitranscriptome and de novo DNA methylation to establish proper heritable epigenetic silencing in human cells.
ER -